Medical treatment with the aminoglycosidic antibiotic gentamicin may produce side effects that include neuromuscular blockage and ototoxicity; which are believed to result from a dysfunction of nicotinic acetylcholine receptors (AChRs). Gentamicin is known to reversibly block ACh-currents generated by the activation of muscle-type alphabetagammadelta-AChR and neuronal alpha9-AChR. We studied the effects of gentamicin on heteromeric alphabetagammadelta-AChR and homomeric alpha7-AChR expressed in Xenopus oocytes. Prolonged treatment with gentamicin, and other antibiotics, differentially altered alphabetagammadelta- and alpha7-AChR responses. Specifically, gentamicin accelerated desensitization and did not reduce ACh-currents in oocytes expressing alphabetagammadelta-AChRs, whereas ACh-currents were reduced and desensitization was unaltered in oocytes expressing alpha7-AChRs. Moreover, acutely applied gentamicin acted as a competitive antagonist on both types of receptors and increased the rate of desensitization in alphabetagammadelta-AChR while reducing the rate of desensitization in alpha7-AChR. This data helps to better understand the action of gentamicin on muscle and nervous tissues, providing mechanistic insights that could eventually lead to improving the medical use of aminoglycosides.

During egestive responses neuron B16 fires at 20 Hz, while neuron B15 is not active. During ingestive responses B16 fires for 0.5-1.0 s at 15-20 Hz, then B15 and B16 fire together, with B15 firing at 7.5-12 Hz. The duration of activity during ingestive responses depends on consumption of food: when food is not consumed, bursts are shorter (e.g. 2 vs 4 s). This study establishes a basis for investigating the role of peripheral neuromodulation under physiologically relevant conditions.

In biology, homeostasis refers to how cells maintain appropriate levels of activity. This concept underlies a balancing act in the nervous system. Synapses require flexibility (i.e. plasticity) to adjust to environmental challenges. Yet there must also exist regulatory mechanisms that constrain activity within appropriate physiological ranges. An abundance of evidence suggests that homeostatic regulation is critical in this regard. In recent years, important progress has been made toward identifying molecules and signaling processes required for homeostatic forms of neuroplasticity. The Drosophila melanogaster third instar larval neuromuscular junction (NMJ) has been an important experimental system in this effort. Drosophila neuroscientists combine genetics, pharmacology, electrophysiology, imaging, and a variety of molecular techniques to understand how homeostatic signaling mechanisms take shape at the synapse. At the NMJ, homeostatic signaling mechanisms couple retrograde (muscle-to-nerve) signaling with changes in presynaptic calcium influx, changes in the dynamics of the readily releasable vesicle pool, and ultimately, changes in presynaptic neurotransmitter release. Roles in these processes have been demonstrated for several molecules and signaling systems discussed here. This review focuses primarily on electrophysiological studies or data. In particular, attention is devoted to understanding what happens when NMJ function is challenged (usually through glutamate receptor inhibition) and the resulting homeostatic responses. A significant area of study not covered in this review, for the sake of simplicity, is the homeostatic control of synapse growth, which naturally, could also impinge upon synapse function in myriad ways. This article is part of the Special Issue entitled 'Homeostatic Synaptic Plasticity'.

This study compares the actions of the intravenous anaesthetics propofol and ketamine on animal behaviour and neuronal activity in the snail Lymnaea stagnalis, particularly in relation to excitatory effects observed clinically. When injected into the whole animal, neither agent induced total anaesthesia. Rather, behavioural activity was enhanced by propofol (10(-5) M) and ketamine (10(-7) M), indicating excitatory effects. When superfused over the isolated central nervous system (CNS), differential effects were produced in two identified neurons, right pedal dorsal 1 (RPeD1) and visceral dorsal 4 (VD4). Resting membrane properties were largely unaffected. However, spike after hyperpolarisation was significantly reduced in RPeD1, but not VD4, with some evidence of increased excitability. In addition, an intrinsic bursting property (post-stimulus burst) in VD4 was altered by propofol (10(-7) M). The results suggest significant excitatory components in the actions of some intravenous anaesthetics, as well as a potential role in modifying excitation and bursting mechanisms in the CNS.

The Drosophila larval neuromuscular junction (NMJ) shares many structural and functional similarities to synapses in other animals, including humans. These include the basic feature of synaptic transmission, as well as the molecular mechanisms regulating the synaptic vesicle cycle. Because of its large size, easy accessibility, and the well-characterized genetics, the fly NMJ remains an excellent model system for dissecting the cellular and molecular mechanisms of synaptic transmission. This protocol describes the steps for performing intracellular recording from fly larval body-wall muscles and explains how to record and analyze spontaneous and evoked synaptic potentials. Methods used include larval dissection (“filleting”), identification of muscle fibers and their innervating nerves, the use of a micromanipulator and microelectrode in penetrating the muscle membrane, and nerve stimulation to evoke synaptic potentials.